The present invention relates to novel tubulysin conjugates and the use thereof in the treatment of cancer diseases.
The tubulysins were for the first time isolated by the group of Höfle and Reichenbach (GBF Braunschweig) from a culture broth of strains of the Myxobacteria Archangium gephyra (F. Sasse et al. J. Antibiot. 2000, 53, 879-885; WO9813375; DE 10008089). These compounds show an extremely high cytotoxic activity against mammalian cell lines with IC50 values in the picomolar range and therefore, are of high interest as potential therapeutics against cancer.

The extremely high cytotoxicity of some tubulysins also exhibits disadvantages: a high general toxicity as well as a low selectivity against normal cells.
The object of the present invention is to lower the toxicity of the tubulysins and to enhance their selectivity.